The proposed work builds on the University of Hawaii 's research strengths in oceanography and tropical medicine and its location in the center of the largest ocean on Earth to create a Pacific Research Center for Marine Biomedicine (PRCMB). Through the collaboration of an interactive milieu of oceanographers and medical researchers, the PRCMB will conduct hypothesis-driven, interdisciplinary research on harmful algal blooms (HAB), water-and vector-borne diseases, and marine-derived pharmaceuticals and probes, in the thematic context of tropical coastal waters and small islands. HAB research will focus on the ciguatera problem, which is unique to the tropics. Specific goals of the research will include (1) a better understanding of the ecology of Gambierdiscus toxicus, with the expectation of identifying management strategies for reducing the frequency of outbreaks, (2) the development of inexpensive, broadly applicable, and rapid methods for testing for the presence of the ciguatoxin in fish, and (3) the development of methods to measure low concentrations of the toxin in humans, with the expectation of determining whether chronic exposure to ciguatoxin may be associated with enigmatic health conditions, such as chronic fatigue syndrome. Research relevant to water-borne pathogens will explore the feasibility of determining human health risks associated with water contact through the direct detection of pathogens in two ways: (1) the use of molecular biological methods to determine the presence, viability, and virulence of a subset of enteric pathogens with the expectation of developing a practical water quality testing protocol based on molecular biological methods and (2) the use of marine bivalves as natural concentrators and sequesters of pathogens with the expectation that the concentration of certain pathogens in bivalves may prove to be a useful diagnostic tool in water quality monitoring. The marine pharmaceutical project will take advantage of recent advances in microbial isolation and culturing methods and the unique and largely unexplored tropical microbial flora surrounding the Hawaiian Islands to (1) isolate and culture marine micro-organisms from tropical coastal and open ocean seas, (2) screen these organisms for the production of antibiotics and other pharmaceuticals with potential public health applications, particularly the treatment of neurodegenerative, cardiovascular, and infectious diseases, and (3) develop molecular genetic tools for the isolation and expression of relevant biosynthetic genes and for expression of pathways in host organisms for the production of marine pharmaceuticals. These research programs will be supported by a core microbial culture and characterization facility that will provide microbial biomass for screening and the isolation of secondary metabolites, develop new enrichment culture isolation techniques, provide and maintain analytical facilities (GC/MS and LC/MS/MS) for PRCMB scientists, and engage faculty from other disciplines in collaborative work with Center investigators. A Pilot Project Program will carry out exploratory research that complements major projects or addresses gaps in the scientific agenda of the PRCMB.